Neural-activity-dependent release of S100B from astrocytes enhances kainate-induced gamma oscillations in vivo.
S100B is the principal calcium-binding protein of astrocytes and known to be secreted to extracellular space. Although secreted S100B has been reported to promote neurite extension and cell survival via its receptor [receptor for advanced glycation end products (RAGE)], effects of extracellular S100B on neural activity have been mostly unexplored. Here, we demonstrate that secreted S100B enhances kainate-induced gamma oscillations. Local infusion of S100B in S100B(-/-) mice enhanced hippocampal kainate-induced gamma oscillations in vivo. In a complementary set of experiments, local application of anti-S100B antibody in wild-type mice attenuated the gamma oscillations. Both results indicate that the presence of extracellular S100B enhances the kainate-induced gamma oscillations. In acutely isolated hippocampal slices, kainate application increased S100B secretion in a neural-activity-dependent manner. Further pharmacological experiments revealed that S100B secretion was critically dependent on presynaptic release of neurotransmitter and activation of metabotropic glutamate receptor 3. Moreover, the kainate-induced gamma oscillations were attenuated by the genetic deletion or antibody blockade of RAGE in vivo. These results suggest RAGE activation by S100B enhances the gamma oscillations. Together, we propose a novel pathway of neuron-glia communications--astrocytic release of S100B modulates neural network activity through RAGE activation.
Sakatani
Seiichi
S
Hirase Research Unit, Neuronal Circuit Mechanisms Research Group, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan. sakatani@brain.riken.jp
Seto-Ohshima
Akiko
A
Shinohara
Yoshiaki
Y
Yamamoto
Yasuhiko
Y
Yamamoto
Hiroshi
H
Itohara
Shigeyoshi
S
Hirase
Hajime
H
D000200:Action Potentials / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D001683:Biological Clocks / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D007074:Immunoglobulin G / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000172:deficiency / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000172:deficiency / Q000502:physiology; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000172:deficiency / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007074:Immunoglobulin G; D009414:Nerve Growth Factors; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579159:S100b protein, mouse; D007608:Kainic Acid